Feeding a choline-devoid diet to rats has been shown to have four distinct but related effects on the induction of hepatocellular carcinomas by chemical carcinogens: 1) a sensitization of the animals to low levels of chemical hepatocarcinogens; 2) a marked reduction in the latent period of hepatocellular carcinoma induction; 3) a high incidence of the tumors; and 4) a change, to liver, of the organ susceptibility of certain chemical carcinogens. The long-term goal of this project is to elucidate the mechanism(s) whereby the dietary regimen modifies so remarkably tumor induction. Studies already performed indicate that a diet devoid of choline exerts a strong promoting action on the evolution of liver cells, initiated by a single exposure to a carcinogen, to foci of pre-neoplastic hepatocytes. At the same time, the diet appears not to affect the initiation stage of liver carcinogenesis. Other studies performed, or in progress, are aimed at elucidating the nature, biochemical properties, and role in the process of hepatocarcinogenesis, of ductular cells and oval cells. Toward this goal, methodologies have been developed for the isolation, separation, and purification of ductular cells and of oval cells of rat liver.